P21-activated kinases 6 (PAK6) associated with many fundamental cellular processes in cancer including cell-cell adhesion, migration and apoptosis. Here, we report a novel function of PAK6 in mitosis. Expression of PAK6 peaks in the M phase. Knockdown of PAK6 increases cell number in G2/M and promotes cell proliferation. PAK6 specifically colocalizes with Eg5 in the centrosome. Depletion of PAK6 results in multipolar spindle and a simultaneous upregulation of Eg5. Further, the PAK6 depletion-induced multiple spindle and cell cycle progression is reversed by knockdown of Eg5. These data suggest that PAK6 regulates spindle formation and cell cycle by regulating Eg5 expression. Additionally, expression of PAK6 is upregulated when Eg5 is downregulated or inhibited. Thus, PAK6 and Eg5 negatively inter-regulate each other. Significantly, the effect of PAK6 expression on the outcome of the HCC patients is controlled by Eg5 expression. Inhibition of Eg5 reverses PAK6 depletion-promoted cell invasion. Collectively, our data indicate that the inter-regulation between PAK6 and Eg5 might promote the progression of HCC.

P21活化激酶6（PAK6）与癌症中的许多基本细胞过程有关，包括细胞粘附，迁移和凋亡。在这里，我们报告PAK6在有丝分裂中的新型功能。PAK6的表达在M期达到峰值。抑制PAK6可增加G2 / M中的细胞数并促进细胞增殖。PAK6与Eg5在中心体中特异性共定位。PAK6的消耗导致多极纺锤体和Eg5的同时上调。此外，通过敲除Eg5逆转了PAK6耗竭诱导的多纺锤和细胞周期进程。这些数据表明PAK6通过调节Eg5表达来调节纺锤体形成和细胞周期。另外，当Eg5被下调或抑制时，PAK6的表达被上调。因此，PAK6和Eg5相互负调控。重要的是 PAK6表达对HCC患者预后的影响由Eg5表达控制。抑制Eg5可逆转PAK6耗竭促进的细胞侵袭。总体而言，我们的数据表明PAK6和Eg5之间的相互调节可能会促进肝癌的发展。